g(m1)-ganglioside and Chagas-Disease

In a previous work, our group reported that Albino Swiss male mice inoculated with T. cruzi to develop acute lethal infection by day 15 decreased parasitemia and survived when treated with total brain gangliosides (GT; 1 mg, daily). In this paper, GT were replaced by GM1 in 0.1 mg dose that caused diminished parasitemia from day 15 to 30 and survival of 80% by day 120 p.i. Treatment with GT 0.15 mg was ineffective. This indicates that GT effect was due to GM1 and that more sialyl residues on the same lipid moiety produces adverse results. GM1 was compared to other sialylated molecules: fetuine and colominic acid. Both of them increased parasitemias and death by day 16 p.i., suggesting that sialic residues favor parasite replication. Asialo-GM1 (0.1 mg daily) was also adverse. This pointed to GM1 not to other ganglioside or sphingolipid or sialoprotein as the active agent. Gangliosides are [Ca+2]i modulators, so GM1 was compared to nifedipine which blocks calcium channels only in the host. Nifedipine treated mice behaved as controls. It is proposed that if GM1 calcium modulation is involved it must be on the parasite rather than on the host. Electrocardiographic (ECG) records show that while infected mice die with bradycardia, treated mice survive and recover normal frequency. Uninfected treated mice showed no electrocardiographic alterations.

Topics: Animals; Calcium Channel Blockers; Chagas Cardiomyopathy; Chagas Disease; Electrocardiography; G(M1) Ganglioside; Heart; Male; Mice; Nifedipine; Parasitemia

Antibodies reactive with the core glycan of asialoganglioside (GA1), monosialoganglioside (GM1), and disialoganglioside (GD1a) were studied in human sera. In healthy individuals, GA1-, GM1-, and GD1a-reactive antibodies were mainly of the IgM class, but also of the IgA and IgG classes, and were present at low titers in the serum of 68%, 79%, and 91% of the individuals studied, respectively. Levels of anti-GA1 and anti-GM1 antibodies, mainly of the IgA and IgG classes, were significantly elevated (P < 0.001) in 62% and 72% of subjects, respectively, chronically infected with Trypanosoma cruzi, with no association found with the degree of myocardial damage. No significant increase in anti-GA1 and anti-GM1 antibodies was found in dilated cardiomyopathy patients. The level of anti-GD1a antibody was not significantly different between healthy controls and chronic chagasic or dilatatory cardiomyopathy patients. Since the peripheral nervous system is very rich in gangliosides, it is possible that the increases in GA1- and GM1-specific antibodies that develop during chronic T. cruzi infection are involved in the pathology of peripheral neuropathy in Chagas' disease.

Topics: Animals; Antibodies, Protozoan; Autoantibodies; Cattle; Chagas Disease; Chronic Disease; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Gangliosides; Glycosphingolipids; Humans; Immunoglobulins; Peripheral Nervous System Diseases